HG-7-85-01 T38653

Product Introduction
Bioactivity


英文名: HG-7-85-01

描述: HG-7-85-01 is a type II ATP competitive inhibitor targeting wild-type and gatekeeper mutations forms of Bcr-Abl, PDGFRα, Kit, and Src kinases. It effectively inhibits T315I mutant Bcr-Abl kinase, as well as KDR and RET kinases with IC50 values of 3 nM, 20 nM, and 30 nM, respectively. In contrast, HG-7-85-01 exhibits weak or no inhibition towards other kinases (IC50 >2 μM). Furthermore, this compound inhibits cell proliferation through the induction of apoptosis and by impeding cell-cycle progression.

体外活性: HG-7-85-01 (0-1 μM; 24 hours; BCR-ABL-, BCR-ABL-T315I-, Kit-T670I-, PDGFRα-T674M-, and PDGFRα-T674I-expressing cells) treatment leads to G0G1 arrest of BCR-ABL-expressing cells[1]. HG-7-85-01 (0-1 μM; 72 hours; BCR-ABL-, BCR-ABL-T315I-, Kit-T670I-, PDGFRα-T674M-, and PDGFRα-T674I-expressing cells) treatment also leads to induction of apoptosis of BCR-ABL-expressing cells[1]. HG-7-85-01 treatment potently and selectively inhibits the proliferation of 32D- and Ba/F3 cells expressing nonmutant BCR-ABL and the BCR-ABL-T315I gatekeeper mutant. HG-7-85-01 shows higher potency against nonmutant BCR-ABL and BCR-ABL-T315I (IC 50 = 0.06-0.14 μM)[1]. HG-7-85-01 inhibits BCR-ABL kinase activity in a concentration-dependent manner, suggesting selective targeting of the BCR-ABL kinase as the mechanism of action of HG-7-85-01[1]. HG-7-85-01 potently inhibits the proliferation of Ba/F3 cells expressing the Kit-T670I gatekeeper mutation (Ba/F3- Kit-T670I) and Ba/F3 cells expressing TEL/PDGFRβ and no effect on parental Ba/F3 cells. HG-7-85-01 inhibits Kit, PDGFR phosphorylation in a concentration-dependent manner[1]. The PDGFRα-T674M and PDGFRα-T674I gatekeeper mutant variants are highly responsive to HG-7-85-01 and significant IL-3 rescue[1]. HG-7-85-01 inhibits the proliferation of Ba/F3 cells transformed with human c-Src (EC 50 = 190 nM), T338I Src (EC 50 = 290 nM), and T338M Src (EC 50 = 150 nM; chicken c-Src numbering). And potently inhibits the proliferation of exon 11 Kit mutant-expressing cells, exon 9 kit mutant-expressing cells are significantly less responsive[1]. Cell Cycle Analysis[1]Cell Line: BCR-ABL-, BCR-ABL-T315I-, Kit-T670I-, PDGFRα-T674M-, and PDGFRα-T674I-expressing cells Concentration: 0 μM, 0.01 μM, 0.1 μM and 1 μM Incubation Time: 24 hours Result: Led to G0G1 arrest of BCR-ABL-expressing cells. Apoptosis Analysis[1]Cell Line: BCR-ABL-, BCR-ABL-T315I-, Kit-T670I-, PDGFRα-T674M-, and PDGFRα-T674I-expressing cells Concentration: 0 μM, 0.01 μM, 0.1 μM and 1 μM Incubation Time: 72 hours Result: Led to induction of apoptosis of BCR-ABL-expressing cells.

体内活性: HG-7-85-01 has limited oral bioavailability (BAV % F mouse = 5 %, rat = 19 %), a moderate half life (T 1/2 mouse =1.1 h rat = 5.8 hours), a relative low maximal serum concentration (C max mouse = 106 ng/mL at 10 mg/kg , rat = 292 ng/mL and 2 mg/kg ) and a relatively high clearance (Cl mouse = 23 ml/min/kg, rat = 13 ml/min/kg)[1].

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

关键字: HG78501 | HG-7-85-01 | HG 7 85 01

HG-7-85-01 T38653信息由TargetMol中国为您提供，如您想了解更多关于HG-7-85-01 T38653报价、型号、参数等信息，欢迎来电或留言咨询。

注：该产品未在中华人民共和国食品药品监督管理部门申请医疗器械注册和备案，不可用于临床诊断或治疗等相关用途